Impact of Dolutegravir Plus Lamivudine as First-line Antiretroviral Treatment on the Human Immunodeficiency Virus Type 1 Reservoir and Inflammatory Markers in Peripheral Blood.

IF 5 2区 医学 Q2 IMMUNOLOGY
Lucía Bailón, Maria C Puertas, Maria C García-Guerrero, Igor Moraes-Cardoso, Ester Aparicio, Yovaninna Alarcón-Soto, Angel Rivero, Elias P Rosen, Jacob D Estes, Julià Blanco, Alex Olvera, Beatriz Mothe, Javier Martinez-Picado, José Moltó
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引用次数: 0

Abstract

Background: To compare the effects of first-line antiretroviral therapy (ART) with dolutegravir plus lamivudine (DTG + 3TC) versus dolutegravir plus emtricitabine/tenofovir alafenamide (DTG + FTC/TAF) on the human immunodeficiency virus type 1 (HIV-1) reservoir and immune activation biomarkers in people with HIV (PWH).

Methods: DUALITY was a 48-week, single-center, randomized, open-label clinical trial in ART-naive PWH, randomized (1:1) to receive ART with DTG + 3TC (2DR group) or DTG + FTC/TAF (3DR group). We measured total and intact proviral HIV-1 DNA, cell-associated RNA in CD4+ T cells, frequency of HIV-infected CD4+ T cells able to produce p24, plasma soluble inflammatory markers, and activation and exhaustion markers in CD4+ and CD8+ T cells.

Results: Forty-four participants (22 per study arm) were enrolled, with baseline mean (standard deviation) log10 plasma viral load (pVL) 4.4 (0.7) copies/mL and CD4+ T-cell counts of 493 (221) cells/μL. At week 48, all participants had pVL <50 copies/mL at week 48, except for 1 participant in the 2DR group who was resuppressed after treating syphilis. Changes from baseline in reservoir parameters and immune biomarkers were comparable between groups.

Conclusions: First-line ART with DTG + 3TC showed similar reductions of HIV-1 persistence parameters and immune markers as DTG + FTC/TAF, supporting DTG/3TC among preferred first-line ART options for PWH.

多罗替韦加拉米夫定作为一线抗逆转录病毒治疗对外周血中 HIV-1 储库和炎症标记物的影响
目的比较多罗替拉韦+拉米夫定(DTG+3TC)与多罗替拉韦+恩曲他滨/替诺福韦-阿拉非那胺(FTC/TAF)一线抗逆转录病毒治疗(ART)对艾滋病病毒感染者(PWH)中 HIV-1 病毒库和免疫激活生物标志物演变的影响:DUALITY是一项为期48周的单中心、随机、开放标签临床试验,以抗逆转录病毒疗法无效的艾滋病病毒感染者为研究对象。参与者被随机(1:1)分配到接受 DTG+3TC 抗逆转录病毒疗法(2DR 组)或 DTG+FTC/TAF 抗逆转录病毒疗法(3DR 组)。对总的和完整的HIV-1病毒DNA、CD4+ T细胞中的细胞相关RNA、能产生p24的HIV感染CD4+ T细胞的频率、血浆可溶性炎症标志物(IL-6、sCD14、TRAIL、IP-10、FABP2、CRP和D-二聚体)以及CD4+和CD8+ T细胞的活化和衰竭标志物进行了纵向测定:共招募了 44 名参与者(每个研究组 22 人)。血浆病毒载量(pVL)和CD4+ T细胞计数的基线平均值(标度)分别为4.4(0.7)拷贝/毫升和493(221)个细胞/立方毫米。所有完成研究的参与者(2DR n=20;3DR n=21)的 pVL 均得出结论:与 DTG+FTC/TAF 相比,DTG+3TC 一线抗逆转录病毒疗法可使外周血中的 HIV-1 持久性参数降低,免疫相关的可溶性和 T 细胞标记物也发生了类似的变化。这些研究结果支持将 DTG/3TC 作为 PWH 一线抗逆转录病毒疗法的首选方案。
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来源期刊
Journal of Infectious Diseases
Journal of Infectious Diseases 医学-传染病学
CiteScore
13.50
自引率
3.10%
发文量
449
审稿时长
2-4 weeks
期刊介绍: Published continuously since 1904, The Journal of Infectious Diseases (JID) is the premier global journal for original research on infectious diseases. The editors welcome Major Articles and Brief Reports describing research results on microbiology, immunology, epidemiology, and related disciplines, on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune responses. JID is an official publication of the Infectious Diseases Society of America.
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